The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From Chemotherapy Treatment (TTX-CINP-201)

A Randomized, Double-Blind, Dose-Finding, Placebo Controlled, Phase II Multicenter Study of Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of many chemotherapeutic agents including vincristine, paclitaxel, cisplatin, oxaliplatin, bortezomib and ixabepilone. Chemotherapy-induced peripheral neuropathy commonly occurs in greater than 40% of patients. To improve the peripheral neuropathy, the chemotherapy dosing is often either decreased or discontinued potentially affecting tumor responsiveness, prognosis, and survival.

There is an unmet medical need for treatment of cancer patients with chemotherapy induced neuropathic pain (CINP) and the proposed study will investigate the efficacy and safety of multiple dose levels of tetrodotoxin (TTX) versus placebo in moderate to severe neuropathic pain caused by chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Pain; Neuropathic Pain; Peripheral Neuropathy
• Intervention / Treatment: Drug: Placebo; Drug: Tetrodotoxin

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Lalita Pandit
    • Fountain Valley, California, United States, 92708
      • Robert Moss
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
    • Los Angeles, California, United States, 90027
      • Global Research Management
    • Los Angeles, California, United States, 90603
      • Innovative Clinical Research
    • Mountain View, California, United States, 94040
      • El Camino Cancer Center
    • Salinas, California, United States, 93901
      • Pacific Cancer Care
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Medical Group
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • St. Vincent's Medical Center
  • Florida
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center
    • Wellington, Florida, United States, 33414
      • Axcess Medical Research
  • Georgia
    • Dublin, Georgia, United States, 31021
      • Cancer Center of Middle Georgia
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center For Cancer and Blood Disorders
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • St. Louis Cancer Care
    • Springfield, Missouri, United States, 65807
      • Mercy Medical Research Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87103
      • New Mexico Oncology Hematology Consultants
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Institute of Pain Research
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390-9179
      • University of Texas Southwestern
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• If female, not of childbearing potential.
• Patients with documented neuropathic pain
• Cancer Patients who have completed a chemotherapy regimen which included taxanes or platinums (or both) and have no evidence actively progressive disease. Concurrent hormonal therapies are allowed
• Patients with stable moderate to severe neuropathic pain
• Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Patients who are able to complete the study-related questionnaires independently in either English or Spanish.

Exclusion Criteria:

• History of peripheral neuropathy attributed to any cause other than chemotherapy.
• Patients receiving any concurrent agents known to cause peripheral neuropathy within 30 days of Randomization.
• Current use of other therapy (ies), including "alternative" therapies, for treatment of peripheral neuropathy within 30 days of Randomization (with the exception of protocol allowed concurrent medications).
• Patients who used controlled release opioids within seven days of baseline period or who expect to use controlled release opioids at any time from baseline to end of study.
• Patients with abnormal kidney function.
• Patients with bone metastases.
• Patients scheduled for treatment for their cancer with chemotherapy or radiotherapy between screening and the end of study visit.
• Current use of lidocaine and other types of antiarrhythmic drugs within 30 days of Randomization.
• Current use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine within 30 days of Randomization.
• Current cause of Chemotherapy Induced Neuropathic Pain attributed to Velcade (Bortezomib) or vinca alkaloids or analogues such as vincristine, vinblasine, vinorelbine and vindesine.
• Current use of tricyclic antidepressant medication, anticonvulsants and monoamine oxidase inhibitors.
• Patients with current uncontrolled asthma or lung disease.
• Patients with significant heart disease.
• Use of an investigational agent within 30 days prior to screening or is scheduled to receive an investigational drug other than TTX during the course of the study.
• Females who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (twice daily); Placebo for injection (1 ml volume), twice a day for four consecutive days.	Drug: Placebo; Sham treatment acting as control arm; Other Names: placebo for injection
Experimental: Low dose Tetrodotoxin (twice daily); Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: Mid-range dose of Tetrodotoxin (twice daily); Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: Max dose Tetrodotoxin (once daily); Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for four consecutive days and Placebo for injection (1 ml volume), once a day in the afternoon for four consecutive days. Total of 4 treatment days.	Drug: Placebo; Sham treatment acting as control arm; Other Names: placebo for injection; Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: Max dose Tetrodotoxin (twice daily); Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28.	The primary efficacy endpoint for Part I was the change from baseline in weekly average NPRS scores at 22 to 28 days after treatment. Baseline was defined as the average of NPRS scores for the last 7 days prior to dosing. Pain was assessed using a Numerical Pain Rating Scale (NPRS) with a range of 0 (no pain) to 10 (extreme pain).	Day 22 to Day 28

Collaborators and Investigators

• Sponsor: Wex Pharmaceuticals Inc.
• Collaborators: Premier Research Group plc
• Investigators: Principal Investigator: Samuel Goldlust, MD, Hackensack University

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): February 11, 2015

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: July 30, 2012
• First Posted (Estimate): August 2, 2012

Study Record Updates

• Last Update Posted (Actual): October 30, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Pain; Chemotherapy; Neuropathy; Puffer fish; Tetrodotoxin; TTX; WEX Pharmaceuticals
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Sodium Channel Blockers; Tetrodotoxin
• Other Study ID Numbers: TTX-CINP-201